Oral–facial–digital syndrome (OFDS) type I in a patient with Werdnig–Hoffman disease

An infant with various craniofacial anomalies was referred to our department at the age of 10 days. She was born as a floppy infant with a symmetrical muscle weakness that was more extensive in the proximal part of the limbs. Her brother had Werdnig– Hoffman disease and died of respiratory failure at the age of 4 months. No family history of malformations was detected. Physical examination revealed the following abnormalities: a high arched palate, micrognathia, a medial cleft of the upper lip, cleft palate, and low set ears (Fig. 1). She also had clinodactyly and partial syndactyly of toes II–III, III–IV on the right foot (Fig. 2). Radiographs of the right foot revealed polydactyly of the first toe. Nail hypoplasia was observed on the bilateral second toes (Fig. 2). No abnormalities were seen on both hands. The face, trunk, and limbs were symmetrical. There was no evidence of abnormalities of the genitalia. Wrinkled skin was conspicuous on the neck and four extremities (Fig. 1). The hair was sparse and brittle. Fine scale and dry skin were conspicuous on the scalp and the upper part of the trunk. Numerous milia were seen on the face. Skin biopsy could not be performed. Hypohidrosis was not found clinically. Because of the accompanying skin manifestations, she was given a diagnosis of oral–facial–digital syndrome (OFDS) type I. Chromosome analysis revealed a normal female karyotype. Chest roentgenogram and a computerized tomographic (CT) scan of the brain detected no abnormal findings. No malformations of the cardiovascular, gastro-intestinal, or urinary systems were detected. Because of the craniofacial anomalies and general muscle weakness, she had feeding problems and had stopped gaining weight at the age of 3 months. She had considerable difficulty in breathing because of chest muscle weakness. Electromyogram (EMG) showed a typical neurogenic pattern. Because of the progressive muscle weakness, typical EMG findings, and a family history, she was diagnosed as having Werdnig–Hoffman disease. Her clinical course was complicated by recurrent pneumonia, apnea, and difficulty with feeding. At the age of 7 months, she died of respiratory failure.